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Biomedical subjects

E Boyer

Publications and source records attributed to E Boyer.

15 recordsLinked to original sources
PubMed2003

Pneumocystis carinii pneumonia in patients with hematologic malignancies: a descriptive study.

Objectives. A retrospective multicentric study was conducted over a five-year period to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating hematologic malignancies.Results. The study included 60 HIV-negative patients with 18 non-Hodgkin's malignant lymphoma (30%), 13 chronic lymphocytic leukaemia (21.7%), 10 acute leukemia (16.6%), 5 multiple myeloma (8.3%), 4 Waldenström's diseases (6.6%), 4 chronic myeloid leukemia (6.6%), 3 myelodysplasia (5%), 2 Hodgkin's diseases (3.3%) and 1 thrombopenia. Bronchoalveolar lavage was diagnostic in all patients. Forty-nine patients received cytotoxic drugs (81.7%), 25 (41.7%) a long-term corticotherapy and 15 (25%) underwent bone marrow transplantation. Twenty-seven patients (45%) required admission in the intensive care unit, 35 (58.3%) received an adjunctive corticotherapy and 18 mechanical ventilation (30%). Twenty patients (33.3%) died of PCP. A previous long-term corticotherapy (p=0.04), high respiratory (p=0.05) and pulse rates (p=0.02), elevated C reactive protein (p=0.01) and mechanical ventilation (OR=13.37; IC: 1.9-50) were associated with a poor prognosis. Adjunctive corticotherapy did not modify the prognosis.Conclusions. These results suggest that PCP can occur during the course of various hematologic malignancies, not only lymphoproliferative disorders. Prognosis remains poor. The diagnosis should be advocated more frequently and earlier to improve the prognosis.

Adult↗
PubMed2002

Acquisition of Mn(II) in addition to Fe(II) is required for full virulence of Salmonella enterica serovar Typhimurium.

The roles of the genes feoB (ABC ferrous iron transporter), mntH (proton-dependent manganese transporter), and sitABCD (putative ABC iron and/or manganese transporter) in Salmonella pathogenicity were investigated by using mutant strains deficient in one, two, or three transporters. Our results indicated that sitABCD encodes an important transporter of Mn(II) and Fe(II) which is required for full virulence in susceptible animals (Nramp1(-/-)) and for replication inside Nramp1(-/-) macrophages in vitro. The mntH sitABCD double mutant (mutant MS) showed minimal Mn(II) uptake and increased sensitivity to H(2)O(2) and to the divalent metal chelator 2,2'-dipyridyl (DP) and was defective for replication in macrophages. In vivo MS appeared to be as virulent as the sitABCD mutant in Nramp1(-/-) animals. The ferrous iron transporter Feo was required for full virulence in 129/Sv Nramp1(-/-) mice, and infection with multiple mutants lacking FeoB was not fatal. The sitABCD feoB mutant (mutant SF) and the mntH sitABCD feoB mutant (mutant MSF) showed minimal Fe(II) uptake and were slightly impaired for replication in susceptible macrophages. MSF showed reduced growth in minimal medium deficient in divalent cations. The role of the mntH gene, which is homologous to mammalian Nramp genes, was also investigated after overexpression in the double mutant MS. MntH preferred Mn(II) over Fe(II) and could suppress MS sensitivity to H(2)O(2) and to DP, and it also improved the intracellular survival in Nramp1(-/-) macrophages. This study indicates that acquisition of Mn(II), in addition to Fe(II), is required for intracellular survival and replication of Salmonella enterica serovar Typhimurium in macrophages in vitro and for virulence in vivo.

Animals↗
PubMed2002

Novel locus required for expression of high-level macrolide-lincosamide-streptogramin B resistance in Staphylococcus aureus.

The yycF1(Ts) mutation in Staphylococcus aureus conferred hypersensitivity to macrolide-lincosamide-streptogramin B (MLS(B)) antibiotics on strains either containing or lacking ermB. The overexpression of the S. aureus Ssa protein restored the yycF1 mutant to wild-type levels of susceptibility. Inactivation of ssa in an unmutagenized strain dramatically reduced ermB-based resistance. Conditional loss of function or expression of ssa in the yycF1 mutant is proposed to result in the observed hypersensitivity to MLS(B) antibiotics.

Amino Acid Sequence↗
PubMed2001

Polyphyletic origins of bacterial Nramp transporters.

The redox-active metals iron and manganese are required for energy metabolism, protection against oxidative stress and defense against infections. In eukaryotes, both divalent metals are transported by Nramp transporters. The sequence of these transporters was remarkably conserved during evolution. Several bacterial Nramp homologs (MntH) are also proton-dependent manganese transporters. Here, we present phylogenetic evidence for the polyphyletic origins of three groups of MntH proteins and for possible Nramp horizontal gene transfer with eukaryotes. We propose that the evolution of the MntH/Nramp family is related to adaptation to oxidative environments, including those arising during infection of animals and plants.

Aerobiosis↗
PubMed1999

Use of a genetic approach to evaluate the consequences of inhibition of efflux pumps in Pseudomonas aeruginosa.

Drug efflux pumps in Pseudomonas aeruginosa were evaluated as potential targets for antibacterial therapy. The potential effects of pump inhibition on susceptibility to fluoroquinolone antibiotics were studied with isogenic strains that overexpress or lack individual efflux pumps and that have various combinations of efflux- and target-mediated mutations. Deletions in three efflux pump operons were constructed. As expected, deletion of the MexAB-OprM efflux pump decreased resistance to fluoroquinolones in the wild-type P. aeruginosa (16-fold reduction for levofloxacin [LVX]) or in the strain that overexpressed mexAB-oprM operon (64-fold reduction for LVX). In addition to that, resistance to LVX was significantly reduced even for the strains carrying target mutations (64-fold for strains for which LVX MICs were >4 microg/ml). We also studied the frequencies of emergence of LVX-resistant variants from different deletion mutants and the wild-type strain. Deletion of individual pumps or pairs of the pumps did not significantly affect the frequency of emergence of resistant variants (at 4x the MIC for the wild-type strain) compared to that for the wild type (10(-6) to 10(-7)). In the case of the strain with a triple deletion, the frequency of spontaneous mutants was undetectable (<10(-11)). In summary, inhibition of drug efflux pumps would (i) significantly decrease the level of intrinsic resistance, (ii) reverse acquired resistance, and (iii) result in a decreased frequency of emergence of P. aeruginosa strains highly resistant to fluoroquinolones in clinical settings.

Anti-Infective Agents↗
PubMed1998

Genotypic changes in human immunodeficiency virus type 1 associated with loss of suppression of plasma viral RNA levels in subjects treated with ritonavir (Norvir) monotherapy.

Ten subjects received 600 to 1,200 mg of the human immunodeficiency virus type 1 (HIV-1) protease inhibitor ritonavir per day. Following 2 weeks of therapy, plasma HIV RNA levels decreased by a mean of 1. 57 (range, 0.89 to 1.96) log units. With continued therapy, HIV RNA levels began to rise in eight subjects. The initial rise in plasma RNA levels was temporally associated with the development and quantitative increase in the V82 resistance mutation. Doubling times of the V82A mutant virus were estimated to be 2.4 to 4.8 days. An L63P/A mutation was commonly present at baseline even in subjects with a durable virologic response. The concomitant acquisition of an L63P/A mutation with the V82A/F mutation at the time when plasma RNA levels rebounded suggests a role for the L63P/A mutation in improving the fitness of the V82A/F mutation. Subsequent additional genotypic changes at codons 54 and 84 were often associated with further increases in plasma RNA levels. Ongoing viral replication in the presence of drugs resulted in the appearance of additional genotypic changes, including the L90M saquinavir resistance mutation, and decreased phenotypic susceptibility. The relative fitness of the protease V82A ritonavir resistance mutation and reverse transcriptase T215Y/F zidovudine resistance mutation following drug withdrawal were estimated to be 96 to 98% that of the wild type. Durability of the virologic response was associated with plasma RNA levels at the nadir. A virologic response beyond 60 days was not observed unless plasma HIV RNA levels were suppressed below 2,000 copies/ml, consistent with estimates from V82A doubling times for selection of a single resistance mutation to dominate the replicating population.

Anti-HIV Agents↗
PubMed1998

[Cutaneous Scedosporium infection revealed by bullous-necrotic purpura].

BACKGROUND: Non-mycetomatous cutaneous scedosprium is an uncommon mycosis observed in immunodepressed subjects. We report a case with an inaugural presentation of bullous and necrotic purpura. CASE REPORT: A 79-year-old man on intermittent corticosteroid therapy for bronchospasm was admitted for bullous and necrotic purpura and fever. Subcutaneous nodules with a sporotrichoid aspect developed despite wide-spectrum antibiotics. Microbiology samples cultured on Sabouraud medium evidenced Scedosporium apiospermum. The pathogenic nature of the infection was proven on a skin biopsy showing numerous myceleal filaments with Gomori-Grocott staining despite negative PAS. No pulmonary involvement was evidenced. The patient was treated unsuccessfully with itraconazole. A Pseudomonas lung infection was fatal. DISCUSSION: Scedosporium apiospermum, an ubiquitous ascomycetes anamorphous to Pseudallescheria boydii, is the cause of a growing number of human infections due to widespread use of immunosuppressors. Skin and lung localizations predominate. The inaugural bullous and necrotic purpural skin manifestations in this case are unusual. In addition, the patient was only minimally immunodepressed and despite demonstrated in vitro sensitivity, itraconazole was ineffective clinically. Treatment is not well defined, but surgery is essential in combination with empirically chosen antifungals.

Aged↗
PubMed1995

Nonisotopic hybridization assay for determination of relative amounts of genotypic human immunodeficiency virus type 1 zidovudine resistance.

A nonisotopic hybridization assay for human immunodeficiency virus genotypic zidovudine resistance determination is described. Biotinylated PCR product was hybridized with enzyme-labeled probes for wild-type or resistant mutant sequences and detected colorimetrically or chemiluminescently in a microplate format. Changes in mutant-to-wild-type ratios allow for the monitoring of longitudinal patient samples.

Antiviral Agents↗
PubMed1995

Determination of human immunodeficiency virus RNA in plasma and cellular viral DNA genotypic zidovudine resistance and viral load during zidovudine-didanosine combination therapy.

Eleven human immunodeficiency virus (HIV)-infected subjects on long-term zidovudine (ZDV) therapy had didanosine (ddI) added to their antiretroviral regimen. HIV RNA in plasma was quantitated by branched-DNA signal amplification assay. Peripheral blood mononuclear cell (PBMC) HIV viral DNA was quantitated by PCR. The relative amounts of wild-type (WT) sequence, ddI resistance-associated codon changes (reverse transcriptase [RT] gene codon 65 K-->R [RT K65R], RT 174V, RT I135K/T/V, and RT M184I/V), and ZDV resistance-associated codon change (RT T215Y/F) from HIV RNA in plasma and RT T215Y/F from PBMC viral DNA were determined by differential hybridization of PCR products from 10 of 11 subjects. All subjects had evidence of RT T215Y/F mutation in both RNA in plasma and PBMC DNA at baseline. Subjects with a mixture of WT and RT T215Y/F HIV RNA in plasma at baseline demonstrated a decline in RNA levels in plasma after the addition of ddI. However, after 6 months of ZDV-ddI therapy, WT HIV RNA in plasma was undetectable in all subjects who had demonstrated a mixture at baseline. Subjects with only RT T215Y/F RNA present in plasma at baseline remained so and demonstrated no decline in RNA levels in plasma. In all subjects, no significant changes in PBMC DNA viral load and RT T215Y/F or WT levels were seen. HIV RNA in plasma demonstrated a significantly higher RT T215Y/F mutant/WT ratio than that of PBMC viral DNA, both at baseline and after ZDV-ddI combination therapy in all subjects. No subjects developed mutations associated with ddI resistance at codons 65, 74, 135, and 184 during this study. This study suggests that determination of relative amounts of RT T215Y/F and WT species from HIV RNA in plasma at baseline may be predictive of virologic response during ZDV-ddI combination therapy.

Base Sequence↗
PubMed1995

[Invasive cysticercosis due to Taenia crassiceps in an AIDS patient].

A first case is reported from France of a subcutaneous and muscular tissues invasion by proliferative larval forms of Taenia crassiceps in an AIDS-patient with severe immunodeficiency. These larvae usually develop in rodents whereas the adult form of the cestode is commonly found in foxes. Authors emphasize the differential diagnosis from other human subcutaneous metacestodoses such as T. solium cysticercosis, cenurosis and hydatidosis. The proliferative aspect of the larvae, the recurrence of lesions after surgical removal and the possible invasion of other tissues are elements of a poor prognosis.

AIDS-Related Opportunistic Infections↗
PubMed1981

[Anatomical sections at low temperature].

The authors present anatomical sections realized with a "scanigraph": an unedited self acting apparatus specially conceived for the exploration of anatomical specimens. It is possible to take photographs of successive parallel plans, scanned at 18, 9 or 6 pictures by millimeter. With the help of a computer, anatomical sections could be reconstituted in orthogonal projection and axial incidence. The results obtained reveal a new process in anatomical investigation.

Anatomy↗
PubMed1977

[The processes of osteotomy in ocular surgery. Introduction of a new type of oscillating osteotome (author's transl)].

The authors recall the different technics of bone approach in the dacryocystorhinostomy, the orbital osteosynthesis, the resilient buckling of the lids, the restoration of the medial palpebral ligament and the orbitotomies by temporal way. The processes that utilize a circular oscillating trephine or a saw with oscillatory motion seem to be suitable to most of these operations. A new type of oscillating osteotome is offered.

Eyelids↗